Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating.

1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz. 2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed. 3. At both frequencies phentolamine (1 mumol/l) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/l) affected mainly the upper part. In the presence of both alpha- and beta-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 mumol/l) did not significantly influence the log dose-response curve of epinine. 4. At 0.5 Hz a submaximal effective concentration of epinine (100 mumol/l) led to an approximately 100% increase of the cyclic AMP level after 60s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 mumol/l). 5. Phentolamine (1 mumol/l) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 nmol/l) completely depressed it. 6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial alpha-adrenoceptors as well as beta-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on alpha-adrenoceptors, whereas in higher concentrations it acts predominantly on beta-adrenoceptors. The positive inotropic effect through beta-adrenoceptor stimulation is mediated by cyclic AMP, while that through alpha-adrenoceptors is not.